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Outline
The purpose of this study was to evaluate the pharmacokinetic behavior and metabolite analysis of a novel anti-triple negative breast cancer candidate compound MT-1 in SD rats. Rats were randomly divided into intragastric gavage group and tail vein injection group. Blood samples were collected at different time points after single dose of MT-1 administration. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established to determine the concentration of MT-1 in plasma with coumarin as the internal standard, and the methodology was verified. The pharmacokinetic parameters were calculated by DAS 2.0 software, and the blood concentration-time curve was drawn by GraphPad Prism 10.1.2 software. At the same time, UPLC-Q-TOF/MSE combined with UNIFI software was used to analyze the metabolites of plasma samples. The results of pharmacokinetic analysis showed that the oral bioavailability of MT-1 was 11.26%, and the absorption was fast. The quantitative range of methodological investigation was 2-800 ng·mL-1, showing a good linear relationship. The matrix effect, extraction recovery, accuracy and stability all met the standards of biological analysis. Metabolite analysis speculated four potential metabolites, mainly involving methylation, cysteine and glucuronic acid binding. This study systematically revealed the pharmacokinetic characteristics and metabolic transformation of MT-1 in vivo, which provided an experimental basis for its further development and application in the treatment of triple-negative breast cancer. This experiment was approved by the Experimental Animal Ethics Committee of Guizhou Medical University. (approval No.: 2503423).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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